MAOIs, monoamine oxidase inhibitors, are a class of prescription medications used to treat depression. They were discovered accidentally in the 1950s, when the MAOI Iproniazid, used to treat tuberculosis, was noted for its ability to lighten mood. At that time, scientists were trying to prove that depression was not simply a state of mind or character flaw, but an illness.

As more people came to acknowledge depression as an illness, more people sought drug therapy. MAOIs, along with tricyclic anti-depressants, were the first to pharmacologically address depression. However, negative and sometimes life-threatening side effects were quite common, and today the first line treatment for depression is a choice of SSRIs, serotonin reuptake inhibitors, because of fewer side effects.

MAOIs work by destroying a protein in the brain and liver called monoamine oxidase. Monoamine oxidase uses up monoamines, which carry three mood-elevating chemicals: serotonin, norepinephrine, and dopamine. By reducing monoamine oxidase, more of these chemicals are allowed to circulate in the brain, thus improving mood. People who suffer from severe depression are thought to have low levels of monoamine, and in these cases, MAOIs can be prescribed to decrease the levels of monoamine oxidase, so the brain can get access to more of the chemicals which elevate mood.

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Unfortunately, another function of monoamine oxidase is to eliminate tyramine, which controls blood pressure. High levels of tyramine without the presence of monoamine oxidase can be fatal, causing sudden spikes in blood pressure. Certain foods naturally introduce tyramine into the bloodstream. Among them are liver, cheese, aged sausages like salami or bologna, and most canned fruits.

While MAOIs were hailed as great wonder drugs upon their discovery, scientists did not understand the connection between the absence of monoamine oxidase and tyramine. As a result, fatalities and near-fatalities occurred among MAOI users and, in some countries, MAOIs were quickly pulled from the market and replaced by tricyclics. Once the tyramine connection was established, MAOIs were re-introduced, but their use is now governed by very strict dietary guidelines.

Avoiding the foods listed above, along with those containing caffeine, comprises only part of the guidelines. MAOIs cannot be combined with allergy medications, many pain medications, most decongestants, most sedatives, tricyclic antidepressants, and illegal drugs like crystal meth and cocaine. Additionally, patients who have exhibited suicidal behaviors in the past are not good candidates for MAOIs because of the extreme risk of fatality if overdose occurs.

Since overdose is so dangerous, children under 16 should not take MAOIs. They are contraindicated in pregnancy because they can pass the placenta, and also should not be used by nursing mothers. MAOIs can cause weigh gain and have a tendency to make users feel "drugged," sleepy, or dizzy. The elderly may especially feel these side effects. MAOIs may also reduce sexual desire. Those with manic depression or bipolar disorder should not take MAOIs since they can suffer from high levels of serotonin, which can cause extreme mania, sleeplessness, and hyperanxiety.

Despite the negative impacts of MAOIs, newer forms like phenelzine, brand name Nardil, are recognized as one of the better options for treating atypical depression, when a patient does not respond to SSRIs. Atypical depression tends to be both more severe and more common than melancholic depression. Mood can be situationally elevated, and those suffering are not constantly depressed, but declining mood results in overeating, oversleeping, and an increased risk of suicide.

Because of the risks associated with MAOIs, patients need to make sure to inform their doctors of all prescription and over the counter medications they use, even if they use these medications only occasionally. Physicians should obtain complete medical histories and determine risk of suicide in patients, and especially rule out bipolar disorders. With vigilance and strict adherence to diet recommendations and contraindications, taking MAOIs in combination with talk therapy can be very helpful in treating depression.

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